Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease

Abstract

We have isolated Clostridium perfringens type B, an epsilon toxin-secreting bacillus, from a young woman at clinical presentation of Multiple Sclerosis (MS) with actively enhancing lesions on brain MRI. This finding represents the first time that C. perfringens type B has been detected in a human. Epsilon toxin’s tropism for the blood-brain barrier (BBB) and binding to oligodendrocytes/myelin makes it a provocative candidate for nascent lesion formation in MS. We examined a well-characterized population of MS patients and healthy controls for carriage of C. perfringens toxinotypes in the gastrointestinal tract. The human commensal Clostridium perfringens type A was present in approximately 50% of healthy human controls compared to only 23% in MS patients. We examined sera and CSF obtained from two tissue banks and found that immunoreactivity to ETX is 10 times more prevalent in people with MS than in healthy controls, indicating prior exposure to ETX in the MS population. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation since these lesions are characterized by BBB permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate.

Gut microbiome analysis in neuromyelitis optica reveals overabundance of Clostridium perfringens

“…Third, it is possible that C. perfringens might participate in more than one CNS autoimmune disease. In this regard, one year after we identified the potential link between C. perfringens and NMO,3 C. perfringens was implicated in MS pathogenesis 19. Another study found that Clostridium species within clusters XIVa and IV, which do not contain C. perfringens (a member of cluster I), are reduced in relapsing–remitting MS patients 20.…”

Gut microbiota composition and relapse risk in pediatric MS: A pilot study

“…Environmental exposures such as stress, season, sunlight, vitamin D and recent viral infections have been linked to risk of relapse, with the presumed pathway(s) being through immune system modulation. Interestingly, these environmental factors also influence the gut microbiota which likewise modulates the immune system which is known to be affected in MS. 1,2,3 Further, differences have been observed in the gut microbiota of individuals with and without MS, 3,5-8 including pediatric MS. 5 Pediatric MS offers opportunity to study disease processes in the very early stages of MS, relatively close to the actual biological onset of disease, potentially limiting confounders. We explored the association between gut microbiota profiles in early pediatric MS and subsequent relapse risk.…”

Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

“…More recently, toxinotype B has been detected in a human with a clinical presentation of multiple sclerosis, providing clues for environment triggers of the disease [4]. C. perfringens toxinotype D affects mainly sheep and lambs but also causes infections in goats and calves [2,3].…”